Bacteriophage Particles to Target the Intestinal Microbiome

Todd Parsley of SynPhaGen, LLC in the U.S. will engineer phage-like particles to transfer genes into specific bacteria in the infant gut that program them to produce therapeutic proteins that protect against environmental enteric dysfunction, which is a major cause of morbidity and mortality in developing countries. Rather than employing bacteria-infecting phage to destroy bacteria, they will engineer safer particles, which are unable to replicate and do not kill the bacterial host. As proof-of-principle, they will modify the defective bacteriophage particles to carry a gene encoding the protein alkaline phosphatase, which keeps the gut healthy in multiple ways including neutralizing bacterial toxins, and program them to infect the bacterium Bacteriodes thetaiotaomicron. The activity of these particles will then be assessed in a mouse model of environmental enteric dysfunction.